Transcription factor Gfi1 restricts B cell-mediated autoimmunity.
The zinc finger transcription factor Gfi1 (growth factor-independent-1) has been involved in various cellular differentiation processes. Gfi1 acts as a transcriptional repressor and splicing control factor upon binding to cognate binding sites in regulatory elements of its target genes. In this study, we report that Gfi1-deficient mice develop autoimmunity. Gfi1-deficient peripheral B cells show a hyperproliferative phenotype leading to expansion of plasma cells, increased levels of nuclear autoantibodies, and Ig deposition in brain and kidneys. Dysregulation of multiple transcription factors and cell cycle control elements may contribute to B cell-dependent autoimmunity. Gfi1 thus emerges as a novel master regulator restricting autoimmunity.
Rathinam
Chozhavendan
C
Department of Pediatric Hematology/Oncology, Hannover Medical School, Hannover, Germany.
Lassmann
Hans
H
Mengel
Michael
M
Klein
Christoph
C
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D016026:Bone Marrow Transplantation / Q000276:immunology; D002455:Cell Division / Q000235:genetics* / Q000276:immunology; D049109:Cell Proliferation; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D007674:Kidney Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D016513:Mice, SCID; D009422:Nervous System Diseases / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D010641:Phenotype; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D001323:Autoantibodies; D004268:DNA-Binding Proteins; C079873:Gfi1 protein, mouse; D014157:Transcription Factors